Hydrate of ilaprazole salt, preparation method thereof and application thereof

Abstract

The invention provides a hydrate of an ilaprazole salt and a preparation method thereof. The hydrate is shown by a formula (I), wherein M is Li, Na or K, n is equal to 1, and x is equal to 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 4.5 or M is Ca, Mg or Zn, n is equal to 2 and x is equal to 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 4.5. The invention also provides application of the hydrate of the ilaprazole salt. Compared with ilaprazole and a salt thereof, the hydrate of the ilaprazole salt can be used as a proton pump inhibitor for treating diseases relevant with disorder in gastric acid secretion, has low side effect, and can be developed to form new clinically-acceptable medicaments. Simultaneously, the preparation method is simple and easy, and repeated experiments prove that the hydrate of the ilaprazole salt has a stable process and can be used for industrial production.

Description

technical field

[0001] The invention belongs to the field of drug synthesis, and in particular relates to a hydrate of ilaprazole salt, a preparation method and application thereof. Background technique

[0002] Proton pump inhibitors of the prazole class, headed by omeprazole, can effectively treat peptic ulcer diseases, such as gastric ulcer, duodenal ulcer, reflux esophagitis and Zoller-Ellison syndrome. Chinese patent application CN1121714 discloses a novel prazole compound——ilaprazole (2-[[(4-methoxy-3-methyl)-2-pyridyl]-methylsulfonyl]-5- (1H-pyrrol-1-yl)-1H-benzimidazole, the structure of which is shown in formula III). The racemate of this compound can be used as a proton pump inhibitor in the treatment of gastric and duodenal ulcer diseases, and shows superior anti-ulcer effect than omeprazole, and the test shows that it is a more superior proton pump Inhibitor.

[0003]

[0004] However, the non-salt form of prazoles is unstable to high temperature and high h...

Examples

Embodiment 1

[0029] Synthesis of Ilaprazole Sodium

[0030] Add 10.0 g (0.0273 mol) of ilaprazole into 50 ml of methanol, heat up to 50° C., add 4.92 g (0.0273 mol) of methanol solution containing 30% (weight) sodium methoxide, stir for 2 hours, cool to 0° C., and filter , the obtained product was dried under reduced pressure at 60° C. to obtain white crystals, i.e. ilaprazole sodium 9.33 g, yield: 88%, content: 99.9%.

[0031] Elemental analysis was performed on the obtained compound: found values: C, 58.63%; H, 4.53%; N, 14.36%; Na, 6.12%; O, 8.21%; S, 8.15%. Theoretical value of ilaprazole sodium: C, 58.75%; H, 4.41%; N, 14.42%; Na, 5.92%; O, 8.24%; S, 8.26%. It can be seen that the ilaprazole sodium compound was prepared by the above method.

Embodiment 2

[0033] Synthesis of Ilaprazole Sodium

[0034] Add 10.0g (0.0273mol) of ilaprazole into 50ml of methanol, heat up to 50°C, add 1.09g (0.0273mol) of sodium hydroxide dissolved in 10ml of methanol, stir for 2 hours, cool to 0°C, and filter to obtain The product was dried under reduced pressure at 60°C to obtain white crystals, i.e. ilaprazole sodium 9.33g, yield: 88%, content: 99.9%.

[0035] Elemental analysis of the obtained compound: found values: C, 58.53%; H, 4.59%; N, 14.35%; Na, 6.05%; O, 8.28%; S, 8.20%. Theoretical value of ilaprazole sodium: C, 58.75%; H, 4.41%; N, 14.42%; Na, 5.92%; O, 8.24%; S, 8.26%. It can be seen that the ilaprazole sodium compound was prepared by the above method.

Embodiment 3

[0037] Synthesis of Ilaprazole Sodium

[0038] Add 10.0 g (0.0273 mol) of ilaprazole into 50 ml of methanol, add 1.09 g (0.0273 mol) of sodium hydroxide, stir at room temperature for 2 hours, concentrate, add n-butanol, and add isopropyl ether to crystallize at room temperature. C and dried under reduced pressure to obtain white crystals, i.e. ilaprazole sodium 9.5g, yield: 90%, content: 99.8%.

[0039] Elemental analysis of the obtained compound: measured value: C, 58.60%; H, 4.57%; N, 14.35%; Na, 6.09%; O, 8.29%; S, 8.10%; C, 58.75%; H, 4.41%; N, 14.42%; Na, 5.92%; O, 8.24%; It can be seen that the ilaprazole sodium compound was prepared by the above method.

technical field

[0001] The invention belongs to the field of drug synthesis, and in particular relates to a hydrate of ilaprazole salt, a preparation method and application thereof. Background technique

[0002] Proton pump inhibitors of the prazole class, headed by omeprazole, can effectively treat peptic ulcer diseases, such as gastric ulcer, duodenal ulcer, reflux esophagitis and Zoller-Ellison syndrome. Chinese patent application CN1121714 discloses a novel prazole compound——ilaprazole (2-[[(4-methoxy-3-methyl)-2-pyridyl]-methylsulfonyl]-5- (1H-pyrrol-1-yl)-1H-benzimidazole, the structure of which is shown in formula III). The racemate of this compound can be used as a proton pump inhibitor in the treatment of gastric and duodenal ulcer diseases, and shows superior anti-ulcer effect than omeprazole, and the test shows that it is a more superior proton pump Inhibitor.

[0003]

[0004] However, the non-salt form of prazoles is unstable to high temperature and high h...

Examples

Embodiment 1

[0029] Synthesis of Ilaprazole Sodium

[0030] Add 10.0 g (0.0273 mol) of ilaprazole into 50 ml of methanol, heat up to 50° C., add 4.92 g (0.0273 mol) of methanol solution containing 30% (weight) sodium methoxide, stir for 2 hours, cool to 0° C., and filter , the obtained product was dried under reduced pressure at 60° C. to obtain white crystals, i.e. ilaprazole sodium 9.33 g, yield: 88%, content: 99.9%.

[0031] Elemental analysis was performed on the obtained compound: found values: C, 58.63%; H, 4.53%; N, 14.36%; Na, 6.12%; O, 8.21%; S, 8.15%. Theoretical value of ilaprazole sodium: C, 58.75%; H, 4.41%; N, 14.42%; Na, 5.92%; O, 8.24%; S, 8.26%. It can be seen that the ilaprazole sodium compound was prepared by the above method.

Embodiment 2

[0033] Synthesis of Ilaprazole Sodium

[0034] Add 10.0g (0.0273mol) of ilaprazole into 50ml of methanol, heat up to 50°C, add 1.09g (0.0273mol) of sodium hydroxide dissolved in 10ml of methanol, stir for 2 hours, cool to 0°C, and filter to obtain The product was dried under reduced pressure at 60°C to obtain white crystals, i.e. ilaprazole sodium 9.33g, yield: 88%, content: 99.9%.

[0035] Elemental analysis of the obtained compound: found values: C, 58.53%; H, 4.59%; N, 14.35%; Na, 6.05%; O, 8.28%; S, 8.20%. Theoretical value of ilaprazole sodium: C, 58.75%; H, 4.41%; N, 14.42%; Na, 5.92%; O, 8.24%; S, 8.26%. It can be seen that the ilaprazole sodium compound was prepared by the above method.

Embodiment 3

[0037] Synthesis of Ilaprazole Sodium

[0038] Add 10.0 g (0.0273 mol) of ilaprazole into 50 ml of methanol, add 1.09 g (0.0273 mol) of sodium hydroxide, stir at room temperature for 2 hours, concentrate, add n-butanol, and add isopropyl ether to crystallize at room temperature. C and dried under reduced pressure to obtain white crystals, i.e. ilaprazole sodium 9.5g, yield: 90%, content: 99.8%.

[0039] Elemental analysis of the obtained compound: measured value: C, 58.60%; H, 4.57%; N, 14.35%; Na, 6.09%; O, 8.29%; S, 8.10%; C, 58.75%; H, 4.41%; N, 14.42%; Na, 5.92%; O, 8.24%; It can be seen that the ilaprazole sodium compound was prepared by the above method.

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